Raised endothelin 1 levels in patients with colorectal liver metastases

BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22). RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.